PO-45

Viral factors and T-cell sensitivity to activation dictate the

loss of control in two cases of HIV-1 viremic non-progressors

Marta Colomer-Lluch, María Pernas, Ruth Peña, Esther Jimenez-Moyano, Judith Dalmau, Concepción Casado,

Cecilio López-Galíndez, Javier Martinez-Picado, and Julia G Prado

Non-pathogenic HIV

VNPsECs

Loss of control (~25%)

Non-pathogenic SIV

Sootey mangabeysAfrican green monkeys

High viral load (104 – 105 copies/mL)Stable CD4+ T cell counts

?

GeSIDA 2019

OBJECTIVE

IrsiCaixa’s VNP cohort: ART-naïve, median CD4 >500 cells/mm3, VL >104 copies/ml, >8 years follow-up

Clinical characteristics of the VNPs

To evaluate the contribution of viral and/or host factors associated

to the loss of control (LoC) in two unusual VNP cases to unravel the

correlates of disease outcome.

GeSIDA 2019

METHODOLOGY

- Replicative capacity assays in pooled CD8-depleted PMBCs

- Viral tropism assays in U87 cell lines (CCR5+ or CXCR4+)

- Phylogenetic analyses of clonal env sequences

GeSIDA 2019

RESULTS1. Enhanced viral fitness is concomitant with a switch in coreceptor usage post-LoC

A. Replicative capacity

B. Viral tropism

GeSIDA 2019

RESULTS2. Coreceptor switch confirmed by clonal env phylogenetic data

VNP-1 VNP-2R5 plasma

R5 plasma isolate

X4 plasma

X4 plasma isolateGeSIDA 2019

RESULTS3. Increased CD4+ and CD8+ T cell susceptibility to activation stimuli post-LoC

A. CD4+ T-cells (72h)

B. CD8+ T-cells (72h)

GeSIDA 2019

RESULTS4. Similar T-cell subsets dynamics after stimuli in pre- and post-LoC samples

A. CD4+ T-cell subsets (72h PHA)

B. CD8+ T-cell subsets (72h PHA)

GeSIDA 2019

RESULTS5. Low CCR5 expression on CD4+ T-cells in VNPs experiencing loss of controlGeSIDA 2019

CONCLUSIONS

• Viral factors, including the selection of particularly aggressive viral strains,

and host factors driving increased susceptibility to activation of CD4+ and

CD8+ T cells are associated with LoC in two cases of VNPs.

Our study reports previously unknown insights into the correlates of disease

outcome in non-pathogenic HIV-1 infection.

PO-45

Julia G Prado

Oscar Blanch

Julieta Carabelli

Esther Jiménez-Moyano

Miguel Marin

Dan Ouchi

Ruth Peña

Bonaventura Clotet

Judith Dalmau

Javier Martínez-Picado

Cecilio López-Galíndez

Concepción Casado

María Pernas

To the patients!

GeSIDA 2019